Suppressive Regulatory T Cell Activity Is Potentiated by Glycogen Synthase Kinase 3β Inhibition

The mechanism by which regulatory T (Treg) cells suppress the immune response is not well defined. A recent study has shown that beta-catenin prolongs Treg cell survival. Because beta-catenin is regulated by glycogen synthase kinase 3 beta(GSK-3 beta)-directed phosphorylation, we focused on GSK-3 beta and the role it plays in Treg cell function. Inhibition of GSK-3 beta led to increased suppression activity by Treg cells. Inhibitor-treated Treg cells exhibited prolonged FoxP3 expression and increased levels of beta-catenin and of the antiapoptotic protein Bcl-xL. Systemic administration of GSK-3 beta inhibitor resulted in prolonged islet survival in an allotransplant mouse model. Our data suggest that GSK-3 beta could be a useful target in developing strategies designed to increase the stability and function of Treg cells for inducing allotransplant tolerance or treating autoimmune conditions.